1. Field of the Invention
The present invention relates to peptides derived from structural gene products of HTLV-I and HTLV-II selected from the group consisting of Env-1 (HTLV-I; a.a. 191-214), Env-2 (HTLV-II; a.a. 187-210), Env-5 (HTLV-I; a.a. 242-257); Gag-1a (HTLV-I; a.a. 102-117) and Pol-3 (HTLV-I; a.a. 487-502), and immunoassays, test kits and vaccines using these peptides.
2. Discussion of Related Art
Human T-cell lymphotropic viruses (HTLV) types I and II are closely related human retroviruses (Wachsman W, Golde DW, Chen ISY. HTLV and human leukemia: Perspectives. Semin Hematol 1986;23:246-56). HTLV-I is etiologically associated with adult T-cell leukemia (ATL) and with a chronic neurologic disorder known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP; (Ehrlich GD, Poiesz BJ. Clinical and molecular parameters of HTLV-I infection. Clin Lab Med 1988;8:65-84). In contrast, HTLV-II, which was first isolated from a patient with a variant of hairy cell leukemia (Kalyanaraman VS, Sarngadharan MG, Robert-Guroff M, et al. A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science 1982;218:571-3), has not been associated with any specific disease (Blattner WA. Retroviruses. In: Evans AS, ed. Viral Infections of Humans: Epidemiology and Control, ed 3. New York: Plenum 1989:545- 92). While HTLV-I infection is endemic in southwestern Japan, the Caribbean, and some regions of Africa (Ehrlich GD, Poiesz BJ. Clinical and molecular parameters of HTLV-I infection. Clin Lab Med 1988;8:65-84), HTLV-II has been reported mainly in intravenous drug users (Lee H, Swanson P, Shorty VS, Zack JA, Rosenblalt JD, Chen I. High rate of HTLV-II infection in seropositive IV drug abusers in New Orleans. Science 1989;244:471-5.) Concern about transmission of HTLV-I/II infection from contaminated blood products has been intensified by serologic evidence of HTLV-I in volunteer blood donors (Williams AE, Fang CT, Slamon DJ, et al. Seroprevalence and epidemiological correlation of HTLV-I infection in U.S. blood donors. Science 1988;240:643-6; Anderson DW, Epstein JS, Lee TH, et al. Serologic confirmation of human T-lymphotropic virus type I infection in healthy blood and plasma donors. Blood 1989;74:2585-91), and the U.S. Food and Drug Administration has suggested HTLV-I screening of all donated blood (Public Health Service working group. Licensure of screening tests for antibody to human T-lymphotropic virus type-I. MMWR 1988;37:736-47; Kaplan JE, Khabbaz RF. HTLV-I: Newest addition to blood donor screening. Am Fam Physician 1989;40:189-95). Recent data from the screening of blood donors indicate that more than half of those seropositive for HTLV-I indeed may be infected with HTLV-II (Chen ISY, Rosenblat JD, Black AC, Arrigo SJ, Green PL. 1990. HTLV-II Prevalence and regulation of gene expression. AIDS Res Hum Retroviruses 6:134-5.) In addition, a high percentage of the HTLV seroreactivity among intravenous drug users in the United States may be due to HTLV-II infection (Lee H, Swanson P, Shorty VS, Zack JA, Rosenblalt JD, Chen I. High rate of HTLV-II infection in seropositive IV drug abusers in New Orleans. Science 1989;244:471-5). In the absence of serological assays that can distinguish HTLV-I from HTLV-II infection (Chen ISY, Rosenblat JD, Black AC, Arrigo SJ, Green PL. 1990. HTLV-II Prevalence and regulation of gene expression. AIDS Res Hum Retroviruses 6:134-5), counseling such individuals about HTLV-I associated diseases may be inappropriate.
The overall structural similarity as well as the identity of much of the primary amino acid sequence (Myers G, Josephs SF, Rabson AB, Smith TF, Wong Staal F. In: Human retroviruses and AIDS. Los Alamos National Laboratory, Los Alamos, N.M. 1988) would suggest antigenic cross-reactivity between HTLV-I and HTLV-II, and indeed, none of the serological assays, to date, can reliably distinguish between these two infections (Anderson DW, Epstein JS, Lee TH, et al. Serologic confirmation of human T-lymphotropic virus type I infection in healthy blood and plasma donors. Blood 1989;74:2585-91; Lee TH, Coligan JE, McLane MF, et al. Serologic cross-reactivity between envelope gene products of type I and type II human T-cell leukemia virus. Proc Natl Acad Sci USA 1984;81:7579). While virus isolation and gene amplification techniques (Lee H, Swanson P, Shortly VS, Zack JA, Rosenblalt JD, Chen I. High rate of HTLV-II infection in seropositive IV drug abusers in New Orleans. Science 1989;244:471-5; De B, Srinivasan A. Detection of human immunodeficiency virus (HIV) and human lymphotropic virus type I or II dual infections by polymerase chain reaction. Oncogene 1989;4:1533-5) can differentiate HTLV-I from HTLV-II infection, these methods are labor intensive and require collection and processing of lymphocytes. A serologic assay that could distinguish the two infections is highly desirable. Such an assay would be very useful both for seroepidemiologic studies that have thus far been hampered by the inability to distinguish the two viruses and for the purpose of counseling blood donors and others who test seropositive (Chen ISY, Rosenblat JD, Black AC, Arrigo SJ, Green PL. 1990. HTLV-II Prevalence and regulation of gene expression. AIDS Res Hum Retroviruses 6:134-5).
Synthetic peptides representing conserved "immunodominant" epitopes provide an attractive alternative to virus-derived antigens in view of their low cost and ability to be accurately reproduced. The analysis of antibodies reactive with predetermined amino acid sequences (Lerner RA. Antibodies of predetermined specificity in biology and medicine. Adv Immunol 1984;36:1-44) has been shown previously to be both a sensitive and specific means to distinguish related retrovirus infections from each other (Norrby E, Biberfeld G, Chiodi F, et al. Discrimination between antibodies to HIV and to related retroviruses using site directed serology. Nature 1987;329:248-50; Gnann JW, McCormick JB, Mitchell S, Nelson JA, Oldstone MBA. 1987. Synthetic peptide immunoassay distinguishes HIV type 1 and HIV type 2 infections. Science 237:1346-9). Because structural proteins such as env, gag and pol from both HTLV-I and HTLV-II are major immunodominant proteins under conditions of natural infection (Lee T, Coligan JE, Homma T, McLane MF, Tachibana N, Essex M. Human T-cell leukemia virus-associated membrane antigens (HTLV-MA): Identity of the major antigens recognized following virus infection. Proc Natl Acad Sci USA 1984;81:3856-60; Kanner SB, Mayer CC, Geffin RB, et al. Human retroviral env and gag polypetides; Serologic assays to measure infection. J Immunol 1986;137:674-8), the present inventors have analyzed the serologic reactivity of those regions of the env, gag and pol of HTLV-I and HTLV-II that exhibited considerable differences in the amino acid sequences (Sodroski J, Patarca R, Perkins D, et al. Sequence of the Envelope glycoprotein gene of Type II human T-lymphotropic virus. Science 1984;225:421-4).
U.S. Pat. No. 4,833,701 discloses a peptide composition having specific immunoreactivity to antibodies to HTLV-I.